To investigate the effect and mechanism of conjugated linoleic acid (CLA) on lipopolysaccharide (LPS)-stimulated microglia inflammatory phenotype transformation. Methods: (1) LPS-stimulated primary microglia cells cultured in vitro were treated with CLA for 24 hours. (2) The PPARγ pathway was inhibited by selective antagonist GW9662, and cells were treated with CLA. The microglia inflammatory phenotype transformation was observed by RT-qPCR and immunofluorescence. Results: (1) The mRNA transcription of IL-6, iNOS, IL-1β, and TNF-α in LPS-stimulated microglia cells was markedly upregulated compared to that of the control group (all P<0.05). Likewise, the protein level of CD16/32 was significantly increased (P<0.05) and that of CD206 was significantly decreased (P<0.05) in the LPS group. (2) Compared to cells with only LPS stimulation, microglia cells with additional CLA treatment dramatically downregulated pro-inflammatory genes (all P<0.05) but upregulated anti-inflammatory genes (all P<0.05). (3) The mRNA transcription and protein expression levels of pro-inflammatory markers in the LPS+CLA+GW9662 group were significantly higher than that of the LPS+CLA group (all P<0.05), while the mRNA transcription and protein expression level of anti-inflammatory markers were significantly lower (all P<0.05). Conclusion: CLA may promote the transformation of LPS-stimulated microglia from the pro-inflammatory to anti-inflammatory phenotype via the PPARγ pathway.